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电针对糖尿病小鼠胃肠动力的促进作用与 CNP/NPR-B-cGMP 和 PDE3A-cGMP 信号通路有关。

Electroacupuncture promotes the gastrointestinal motility of diabetic mice by CNP/NPR-B-cGMP and PDE3A-cGMP signaling.

机构信息

Division of Gastroenterology, Union Hospital, Tongji medical college, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Neurogastroenterol Motil. 2019 Apr;31(4):e13539. doi: 10.1111/nmo.13539. Epub 2019 Jan 22.

Abstract

BACKGROUND

Electroacupuncture (EA) can promote gastrointestinal (GI) motility of diabetic mice, but the mechanism is not clearly elucidated. Natriuretic peptides (NPs) were related to the diabetes-induced gut dysfunction of mice, which may be associated with ICC (interstitial cells of cajal). Besides, EA could increase the ICC of diabetic mice. Our aim was to explore whether EA can promote the gut motility by CNP/NPR-B-cGMP and PDE3A-cGMP signaling in diabetic mice, and the relationship between NPs and ICC.

METHODS

Wild C57BL/6 male mice were divided into five groups: control group, diabetic mellitus (DM group), diabetic mellitus plus sham EA group (SEA), diabetic mellitus plus low-frequency EA group (LEA), and diabetic mellitus plus high-frequency group (HEA). Gastrointestinal motility was assessed by gastric emptying and GI transit test. Immunofluorescence staining was applied to assess the expression level of CNP, NPR-B, and c-Kit. Western blot, PCR, and ELISA were used to detect the level of CNP, NPR-B, PDE2A, PDE3A, c-Kit, mSCF, and cGMP content. The correlativity between NPR-B and mSCF was evaluated by Pearson's correlation and linear regression analyses.

KEY RESULTS

(a) EA could improve the GI dysfunction of diabetic mice. (b) CNP, NPR-B, and cGMP contents were decreased, but the level of PDE3A, c-Kit, and mSCF was increased in the EA groups. (c) There was a negative correlation between NPR-B and mSCF among the groups.

CONCLUSIONS AND INFERENCES

Electroacupuncture promotes the GI function by CNP/NPR-B-cGMP and PDE3A-cGMP signaling in diabetic mice; up-regulated mSCF/c-Kit signaling by EA may be mediated partially via down-regulation of CNP/NPR-B signaling.

摘要

背景

电针(EA)可促进糖尿病小鼠的胃肠(GI)蠕动,但机制尚不清楚。利钠肽(NPs)与糖尿病诱导的小鼠肠道功能障碍有关,可能与 ICC(Cajal 间质细胞)有关。此外,EA 可增加糖尿病小鼠的 ICC。我们的目的是探讨 EA 是否可以通过 CNP/NPR-B-cGMP 和 PDE3A-cGMP 信号促进糖尿病小鼠的肠道蠕动,以及 NPs 与 ICC 之间的关系。

方法

将野生 C57BL/6 雄性小鼠分为五组:对照组、糖尿病(DM 组)、糖尿病加假电针(SEA)组、糖尿病加低频电针(LEA)组和糖尿病加高频电针(HEA)组。通过胃排空和 GI 转运试验评估胃肠动力。免疫荧光染色用于评估 CNP、NPR-B 和 c-Kit 的表达水平。Western blot、PCR 和 ELISA 用于检测 CNP、NPR-B、PDE2A、PDE3A、c-Kit、mSCF 和 cGMP 含量。通过 Pearson 相关和线性回归分析评估 NPR-B 与 mSCF 之间的相关性。

主要结果

(a)EA 可改善糖尿病小鼠的 GI 功能障碍。(b)CNP、NPR-B 和 cGMP 含量降低,但 EA 组 PDE3A、c-Kit 和 mSCF 水平升高。(c)各组 NPR-B 与 mSCF 呈负相关。

结论和推论

电针对糖尿病小鼠的 GI 功能具有促进作用,其机制可能与 CNP/NPR-B-cGMP 和 PDE3A-cGMP 信号有关;EA 上调的 mSCF/c-Kit 信号可能部分通过下调 CNP/NPR-B 信号介导。

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